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Polynorbornene-goniothalamin and polynorbornene-piplartine conjugates for cancer therapy

Grant number: 18/24020-4
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 15, 2019
Effective date (End): February 14, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal researcher:Ronaldo Aloise Pilli
Grantee:Carolyne Brustolin Braga
Supervisor abroad: Marcus Weck
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: New York University, United States  
Associated to the scholarship:17/06146-8 - Development of nanocarriers based on dendrimers and polymer nanoparticles for selective delivery of goniothalamin, piplartine and Monastrol, BP.PD

Abstract

Natural products have been the major source of inspiration for the development of novel drugs for cancer treatments. In particular, several studies have highlighted the potential of goniothalamin (GTN) and piplartine (PPT), natural products found in plants, for cancer therapy. However, their low water solubility, and significant toxicity towards healthy cells can severely limit their application as therapeutic agents. Recent advances have shown that the use of nanomaterials as drug delivery systems represents a promising strategy to overcome these limitations. In addition to target the delivery of drugs to tumor tissues, nanomaterials can enhance the water solubility, stability, circulating half-life, biodistribution, and therapeutic index of the bioactive molecules. Considering the potential of polynorbornenes as polymeric carriers, and in connection with our interests of increasing selectivity and potency of goniothalamin and piplartine towards cancer cells, this project aims the development of new multifunctional and biocompatible polymer-drug conjugates with very low polydispersities based on polynorbornenes for the selective delivery of these two bioactive compounds to tumor cells. We will focus on the synthesis of the new nanomaterials, their functionalization with the two aforementioned natural products, their complete structural characterization, and evaluation of their in vitro behavior. We will explore the self-assembly process of the new materials for the construction of an idealized nanosystem for drug delivery applications. The cytotoxic activities of all proposed nanosystems will be compared to define structure-activity relationships towards cancer cells. (AU)

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